AIMTo investigate the complexation of prostaglandin E1 (PGE1) with hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solutions, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters during the complexation process.

METHODSThe measurements of the complexation mechanism, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters were carried out by the following methods separately: phase solubility method, UV absorption spectroscopy, circular dichroism spectroscopy, equimolar series method and thermodynamic method, respectively.

RESULTSThat all the phase solubility diagrams showed a typical AL-type in various pH buffered solutions, suggested the formation of a soluble complex of 1:1 molar ratio. Both UV absorption spectroscopy and circular dichroism spectroscopy confirmed that the significant interaction between the host and guest molecules was probably due to the inclusion of chromophore moiety of PGE1 molecule into the hydrophobic cavity of HP-beta-CD molecule. The change in the thermodynamic parameters suggested that the complexation could proceed spontaneously along with the release of heat and the decrease of entropy.

CONCLUSIONAn 1:1 molar ratio inclusion complex of PGE1 with HP-beta-CD could be formed spontaneously and, hence, the solubility of PGE1 in aqueous solution increased. Appropriate temperature and suitable media pH probably favor the progress of complexation procedure.

2-Hydroxypropyl-beta-cyclodextrin ; Alprostadil ; administration & dosage ; chemistry ; Hydrogen-Ion Concentration ; Solubility ; Technology, Pharmaceutical ; methods ; Temperature ; beta-Cyclodextrins ; administration & dosage ; chemistry

The exact etiology and pathogenesis of knee osteoarthritis (KOA) are still unknown and it is hard to treat the disease fundamentally. With new therapeutic methods and techniques appearing, the present situation of treating the disease will be changed in the near future. Basic research of knee osteoarthritis will contribute to clarifying the pathogenesis and exploring the therapeutic methods. This article makes a brief review on the up-to-date basic researches of knee osteoarthritis by reviewing literature concerned in recent years.
Animals ; Cytokines ; physiology ; Disease Models, Animal ; Genetic Therapy ; Humans ; Metalloproteases ; physiology ; Osteoarthritis, Knee ; etiology ; therapy ; Stem Cell Transplantation ; Tissue Engineering

The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE, was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area under the blood pressure decrease percent-time curves (AUC, % x min) were determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip), and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal approximately = im > ip > sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal > im approximately = ip > sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.
Administration, Intranasal ; Administration, Sublingual ; Alprostadil ; administration & dosage ; pharmacokinetics ; pharmacology ; Animals ; Area Under Curve ; Biological Availability ; Blood Pressure ; drug effects ; Dose-Response Relationship, Drug ; Injections, Intramuscular ; Injections, Intraperitoneal ; Injections, Intravenous ; Male ; Rats ; Rats, Wistar

To study the effect of Panax notoginseng saponins (PNS) on liver drug metabolic enzyme activity, mRNA and protein expressions in rats. Male Wistar rats were randomly divided into nine groups. After administration of the test drugs, their liver microsomes, liver total RNA and total protein were extracted to detect the regulating effect of PNS on liver drug metabolic enzyme activity-related subtype enzymatic activity, mRNA and protein expression by substrate probe, quantitative PCR and Western Blot technology. The result of this experiment was that PNS could significantly induce CYP1A2 and CYP2E1 enzyme activity, mRNA expression, CYP2E1 protein expression level. PNS significantly induced CYP3A mRNA expression, but with no significant effect in CYP3A enzyme activity level. PNS had no significant effect CYP1A1 and CYP2B mRNA expressions and enzyme activity levels. PNS had selective regulations on different P450 subtypes, and the major subtypes were CYP1A2 and CYP2E1. In clinical practice, particularly in the combination with CYP1A2 and CYP2E1 metabolism-related drugs, full consideration shall be given to the possible drug interactions in order to avoid potential toxic and side effects. Meanwhile, whether the induction effect of CYP2E1 gets involved in ginsenoside's effect incavenging free radicals deserves further studies.
Animals ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Liver ; drug effects ; enzymology ; Male ; Microsomes, Liver ; drug effects ; enzymology ; Panax notoginseng ; chemistry ; Rats, Wistar ; Saponins ; pharmacology